RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators

The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. There is increasing evidence for important functional interactions between the miRNA and nuclear receptor (NR) signaling networks, with recent data showing that estrogen, acting through the estrogen receptor, can modulate initial aspects of nuclear miRNA processing. Here, we show that the cytoplasmic RISC proteins PACT, TRBP, and Dicer are steroid receptor RNA activator (SRA) binding NR coregulators that target steroid-responsive promoters and regulate NR activity and downstream gene expression. Furthermore, each of the RISC proteins, together with Argonaute 2, associates with SRA and specific pre-microRNAs in both the nucleus and cytoplasm, providing evidence for links between NR-mediated transcription and some of the factors involved in miRNA processing.

[1]  T. Gambichler,et al.  Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA‐induced silencing complex (RISC) components argonaute‐1, argonaute‐2, PACT, TARBP1, and TARBP2 in epithelial skin cancer , 2012, Molecular carcinogenesis.

[2]  B. O’Malley,et al.  Nuclear receptor coregulators: modulators of pathology and therapeutic targets , 2012, Nature Reviews Endocrinology.

[3]  P. Leedman,et al.  Steroid Receptor RNA Activator - A nuclear receptor coregulator with multiple partners: Insights and challenges. , 2011, Biochimie.

[4]  Zhihong Yang,et al.  Regulation of microRNA expression and function by nuclear receptor signaling , 2011, Cell & Bioscience.

[5]  S. Au,et al.  The double-stranded RNA-binding protein PACT functions as a cellular activator of RIG-I to facilitate innate antiviral response. , 2011, Cell host & microbe.

[6]  S. Ivashuta,et al.  Posttranscriptional gene silencing in nuclei , 2010, Proceedings of the National Academy of Sciences.

[7]  Didier Picard,et al.  Multidirectional interplay between nuclear receptors and microRNAs. , 2010, Current opinion in pharmacology.

[8]  Ruchir R. Shah,et al.  Glucocorticoids Modulate MicroRNA Expression and Processing during Lymphocyte Apoptosis* , 2010, The Journal of Biological Chemistry.

[9]  W. Filipowicz,et al.  Dicer Is Associated with Ribosomal DNA Chromatin in Mammalian Cells , 2010, PloS one.

[10]  Bert W O'Malley,et al.  Research resource: expression profiling reveals unexpected targets and functions of the human steroid receptor RNA activator (SRA) gene. , 2010, Molecular endocrinology.

[11]  B. O’Malley,et al.  Maturation of microRNA is hormonally regulated by a nuclear receptor. , 2009, Molecular cell.

[12]  Z. Paroo,et al.  Phosphorylation of the Human MicroRNA-Generating Complex Mediates MAPK/Erk Signaling , 2009, Cell.

[13]  G. Hannon,et al.  The estrogen receptor-α-induced microRNA signature regulates itself and its transcriptional response , 2009, Proceedings of the National Academy of Sciences.

[14]  G. Peters,et al.  The double-stranded RNA-binding protein, PACT, is required for postnatal anterior pituitary proliferation , 2009, Proceedings of the National Academy of Sciences.

[15]  Guohua Wang,et al.  Estradiol-regulated microRNAs control estradiol response in breast cancer cells , 2009, Nucleic acids research.

[16]  Carla Oliveira,et al.  A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function , 2009, Nature Genetics.

[17]  D. Bartel.  MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[18]  C. Tepper,et al.  microRNAs and prostate cancer , 2008, Journal of cellular and molecular medicine.

[19]  B. White,et al.  The Micro-Ribonucleic Acid (miRNA) miR-206 Targets the Human Estrogen Receptor-α (ERα) and Represses ERα Messenger RNA and Protein Expression in Breast Cancer Cell Lines , 2007 .

[20]  Rajiv Dhir,et al.  Up-regulation of dicer, a component of the MicroRNA machinery, in prostate adenocarcinoma. , 2006, The American journal of pathology.

[21]  K. Jeang,et al.  HIV-1 TAR RNA Subverts RNA Interference in Transfected Cells through Sequestration of TAR RNA-binding Protein, TRBP* , 2006, Journal of Biological Chemistry.

[22]  D. Corey,et al.  Involvement of AGO1 and AGO2 in mammalian transcriptional silencing , 2006, Nature Structural &Molecular Biology.

[23]  Xuemei Wang,et al.  Alternative splicing of the first intron of the steroid receptor RNA activator (SRA) participates in the generation of coding and noncoding RNA isoforms in breast cancer cell lines. , 2006, DNA and cell biology.

[24]  J. Qin,et al.  Molecular basis for PKR activation by PACT or dsRNA. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Lanz,et al.  SLIRP, a small SRA binding protein, is a nuclear receptor corepressor. , 2006, Molecular cell.

[26]  K. Hirose,et al.  A role of the double-stranded RNA-binding protein PACT in mouse ear development and hearing. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[27]  V. Kim,et al.  The role of PACT in the RNA silencing pathway , 2006, The EMBO journal.

[28]  Anne Gatignol,et al.  TRBP, a regulator of cellular PKR and HIV‐1 virus expression, interacts with Dicer and functions in RNA silencing , 2005, EMBO reports.

[29]  R. Shiekhattar,et al.  TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing , 2005, Nature.

[30]  T. Rana,et al.  Specific and potent RNAi in the nucleus of human cells , 2005, Nature Structural &Molecular Biology.

[31]  R. Lanz,et al.  Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA) , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. C. James,et al.  Quantitative assessment of gene targeting in vitro and in vivo by the pancreatic transcription factor, Pdx1. Importance of chromatin structure in directing promoter binding. , 2002, The Journal of biological chemistry.

[33]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[34]  B. Williams,et al.  NF-κB Activation by Double-Stranded-RNA-Activated Protein Kinase (PKR) Is Mediated through NF-κB-Inducing Kinase and IκB Kinase , 2000, Molecular and Cellular Biology.

[35]  Neil J McKenna,et al.  A Steroid Receptor Coactivator, SRA, Functions as an RNA and Is Present in an SRC-1 Complex , 1999, Cell.

[36]  B. Berkhout,et al.  Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR. , 1991, Science.

[37]  B. Peterlin,et al.  7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcription , 2012, Wiley interdisciplinary reviews. RNA.

[38]  B. Williams,et al.  Structure and function of the protein kinase R. , 2007, Current topics in microbiology and immunology.

[39]  B. Williams,et al.  NF-kappaB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-kappaB-inducing kinase and IkappaB kinase. , 2000, Molecular and cellular biology.